How Methadone and Buprenorphine Work to Prevent Relapse

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Drug-related convictions place a substantial burden on the criminal justice system and on society. The MD Magazine Peer Exchange “Medication-Assisted Treatment in Drug Abuse Cases: A Path to Success” features a panel of experts in the criminal justice field who provide insight on medication-assisted re-entry programs.

This Peer Exchange is moderated by Peter Salgo, MD, professor of medicine and anesthesiology at Columbia University College of Physicians and Surgeons, and an associate director of Surgical Intensive Care at New York-Presbyterian Hospital.

The panelists are:

• Phillip Barbour, master trainer with the Center for Health and Justice at Treatment Alternatives for Safe Communities, in Chicago, IL
• Jac Charlier, director for consulting and training, also with the Center for Health and Justice at Treatment Alternatives for Safe Communities, in Chicago, IL
• Jonathan Grand, MSW, LICSW, senior program associate at the Advocates for Human Potential in Sudbury, MA
• Joshua Lee, MD, MSc, associate professor in the Department of Population Health, and a research clinician at Bellevue Hospital Center, NYU Langone Medical Center, and the New York City jails

Peter L. Salgo, MD: We’ve been dancing around it, and I alluded to it: how does methadone work?

Joshua D. Lee, MD, PhD: So, you have, in your brain, opiate receptors. One particular one is the mu opiate receptor that plugs in to our reward center. A bunch of heroin, at that receptor, feels great. “I get high. I have no pain. I’m relaxed, not anxious,” or, “I took too much and I get sleepy and go into a coma.” But the reinforcing good things about heroin are driven through this one opiate receptor. And heroin, there is what’s called a full agonist, meaning it goes there and it does everything. Other full agonists are oxycodone, morphine, Dilaudid (hydromorphone), and methadone.

And then there’s differences in that pharmacopeia of opiate agents: how long acting they are, how they’re absorbed, and how they’re dosed. The ones that are usually abused are short-acting. They don’t last very long, but they give you a rush, also, in terms of how you administer them. So, you crush and snort oxycodone or you inject, smoke, or sniff the heroin. That gets into your system pretty quickly. You get a big rush and then it starts to go away fairly rapidly over the course of a couple hours.

Whereas methadone is also an opiate. You’re going to be physically dependent on opiates, but you’re going to get it by an oral dose that’s going to go to your stomach, then to your liver, and then to your brain. It takes a while. It’s a very long-lasting process. It’s in your system for 1 to 3 days. Once you build up to a maintenance dose, like in a program, you really have it in your system for weeks, or even months, in terms of active drug levels, and it goes to the receptor.

Methadone, it turns out, goes to that same place that heroin works, but it sits there. It doesn’t do as much, but it sits there for a long time so you don’t get sick. “I’m getting sick. I got a fix again. Now, I have methadone. I’m okay for today, and I can sleep tonight. And I wake up the next morning and I’m not sick.” So, it gets you out of the cycle of having to dose a short-acting opiate all the time, and it outcompetes heroin at the receptor. It has a stronger chemical affinity, it’s stickier at the receptor, and the heroin then comes on board. You took your dose of methadone this morning, and then, for some reason, you’re using heroin later that day. You just don’t get much heroin effect; it’s a blocker at that point. That’s how it works.

Peter L. Salgo, MD: And there’s no euphoria from methadone?

Phillip Barbour: There could be. In the beginning, there usually is. When they try to adjust it to where they know where the blocking dose winds up being, a lot of clients often will go to what are called Pay Clinics; at least in Chicago, that’s how it works. They’re actually dosed at very, very high levels, probably much higher than they actually need, to block the effects in those opioid receptors. So, yes, in the beginning, there’s some euphoria, but you quickly develop a tolerance.

But one of the other things that I wanted to mention is, ironically, Peter, when I got clean and got out of treatment, I went and became a certified substance abuse counselor. Why not? What else am I going to do? And my very first job was at a methadone program to which 80% of my caseload was in noncompliance, meaning they were on the program, they would get their doses, and in some cases, they got pickups. They’d be good enough for a little while to get pickups for a couple of days. That’s where you take a dose at the window and take your next two doses home with you. But, they would go out and divert it, and then sell it on the street to go buy the heroin so they could feel that euphoria.

The other part about opiate addiction was, especially for heroin addicts that inject the drug, there’s a link to the ritual of fixing as there is to the actual effects of the drug. For a lot of them, getting high was the low point of the day; it was all the stuff they had to go through to get the money and to go cop. You had to deal with both things: the physical aspects of heroin addiction and that mental attachment to the lifestyle.

Peter L. Salgo, MD: So, even with methadone, you’ve got to do a two-pronged approach.

Phillip Barbour: Absolutely.

Joshua D. Lee, MD, PhD: You’ve got to be into it.

Peter L. Salgo, MD: And you were talking about buprenorphine. How does that differ from methadone?

Joshua D. Lee, MD, PhD: Let me correct: methadone could be euphoric and abused. If I gave it to Charlie right now, you’d feel narked up all of a sudden. But for people coming to a clinic who are already addicted to opiates, it’s typically not a whole lot of fun or euphoric or getting people high. So, it does have abuse potential. It’s partly why we regulate it and dispense it in certain clinics every day, but you don’t get take-home doses or 90 days’ worth from CVS. It has some abuse potential, but mostly, it’s not abused by people that are seeking treatment. Buprenorphine goes to the same opioid receptor. It’s very sticky, long lasting, but it’s what we call a “partial agonist.” Methadone, if I kept the dose going up, the opiate effects would go up and eventually you’d stop breathing. So, it has a risk profile and a potential for overdose.

Peter L. Salgo, MD: As an anesthesiologist, I’d just like to say, that’s bad.

Joshua D. Lee, MD, PhD: Yes, that is bad. We use it carefully only in these certain clinical environments. Buprenorphine is a partial agonist. The dose of buprenorphine goes up, and only to a point do I have opiate effects. Then, I don’t really get many more. There’s a plateau of opiate effects, and it turns out to be very, very hard to overdose on buprenorphine.

Peter L. Salgo, MD: So, it’s safer?

Joshua D. Lee, MD, PhD: It’s much safer. If people have 30 days’ worth in their medicine cabinet and they take all of it at once in an overdose setting, intentional or not, they are unlikely to have a fatality.

Peter L. Salgo, MD: Is it fair to say then, these medications that we’ve been talking about play an essential role? They’re effective if people use them?

Joshua D. Lee, MD, PhD: Of course.

Peter L. Salgo, MD: And then, of course, sometimes they don’t or they divert them. But, if you use them, they can really help.